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PMID: 12393746 Published · ppublish English Clinical Trial Comparative Study Journal Article Multicenter Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461).

Blood ·Vol. 100 ·No. 13 ·2002-12-15 ·Pages 4325-36

Byrd JC, Mrózek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, Pettenati MJ, Patil SR, Rao KW, Watson MS, Koduru PR, Moore JO, Stone RM, Mayer RJ, Feldman EJ, Davey FR, Schiffer CA, Larson RA, Bloomfield CD, Cancer and Leukemia Group B CALGB 8461

Abstract

We analyzed prospectively 1213 adults with de novo acute myeloid leukemia (AML) to ascertain the prognostic impact of cytogenetic abnormalities on complete remission (CR) rate, 5-year cumulative incidence of relapse (CIR), and 5-year overall survival (OS). All patients received similar induction therapy. Median follow-up for surviving patients was 8.3 years. Nonprioritized cytogenetics distinguished t(8;21) and inv(16)/t(16;16) as conferring a significantly better prognosis than normal karyotype. Prognostic impact of many abnormalities could not be determined independently because of their association with complex karyotype. Neither complex karyotype nor secondary aberrations affected outcome of patients with t(8;21), inv(16)/t(16;16), or t(9;11). Among other patients, those with complex karyotypes had significantly worse outcomes than cytogenetically normal patients. Based on outcome for specific cytogenetic abnormalities and karyotype complexity, patients were divided into 3 risk groups: favorable (CR 88%, CIR 54%, OS 55%), intermediate (CR 67%, CIR 67%, OS 24%), and adverse (CR 32%, CIR 92%, OS 5%). Multivariate analyses confirmed the major contribution of cytogenetics to the probability of attaining CR, CIR, and OS. For the adverse-risk group, the probability of achieving CR was 4.0 and 11.9 times lower, the probability of relapse 3.0 and 4.4 times higher, and the risk of death 2.1 and 4.3 times higher than those for the intermediate and favorable groups, respectively. We conclude that although the prognostic impact of many recurring abnormalities has not been ascertained independently of complex karyotype, cytogenetics is among the most useful factors predicting attainment of CR, CIR, and long-term survival in adult AML.

MeSH Terms
Acute Disease Adult Antineoplastic Combined Chemotherapy Protocols/administration & dosage,therapeutic use Chromosome Aberrations Chromosome Inversion Chromosomes, Human/ultrastructure Cytarabine/administration & dosage Daunorubicin/administration & dosage Disease-Free Survival Follow-Up Studies Humans Incidence Karyotyping Leukemia, Myeloid/drug therapy,genetics,mortality Life Tables Prospective Studies Recurrence Remission Induction Risk Factors Survival Analysis Translocation, Genetic Treatment Outcome Trisomy
Chemicals
Cytarabine Daunorubicin
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Byrd John C
Division of Hematology and Oncology, Comprehensive Cancer Center, The Ohio State University, Columbus 43210-1240, USA. byrd-3@medctr.osu.edu
Mrózek Krzysztof
Dodge Richard K
Carroll Andrew J
Edwards Colin G
Arthur Diane C
Pettenati Mark J
Patil Shivanand R
Rao Kathleen W
Watson Michael S
Koduru Prasad R K
Moore Joseph O
Stone Richard M
Mayer Robert J
Feldman Eric J
Davey Frederick R
Schiffer Charles A
Larson Richard A
Bloomfield Clara D
Cancer and Leukemia Group B (CALGB 8461)
Supplementary Concepts
HDAC protocol (Protocol)
Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
Published
2002-12-15
Epub
2002-00-01
Pages
4325-36
Language
English
Region
United States
NLM ID
7603509
Subset
IM
Grants
NCI NIH HHS · CA 77658 · United States
NCI NIH HHS · CA16058 · United States
NCI NIH HHS · CA31946 · United States
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